Imaging agents for monitoring changes of dopamine receptors and methods of using thereof
The present invention is related generally to a method for screening subjects to determine those subjects more likely to develop diabetes by quantization of insulin producing cells. The present invention is also related to the diagnosis of diabetes and related to monitor disease progression or treatment efficacy of candidate drugs.
1. A non-invasive method of monitoring changes in beta cell mass in a subject comprising:
detecting a first time point level of Dopamine receptor expression in endocrine pancreatic islets in the pancreas of said subject,
detecting a second time point level of Dopamine receptor expression in endocrine pancreatic islets in the pancreas of said subject, and
monitoring change in beta cell mass by comparing the first time point level of Dopamine receptor expression with the second time point level of Dopamine receptor expression,
wherein a reduction of Dopamine receptor expression in endocrine pancreatic islets in the pancreas of said subject is indicative of reduction in beta cell mass, and wherein each of said detecting the first time point level and second time point level comprises an assay comprising the steps of:
a. administering 18 F-fallypride capable of binding with a high level of specificity to a D2-like receptor into said subject in the presence of haloperidol;
b. measuring an imaging signal of 18 F-fallypride in the pancreas of said subject in the presence of haloperidol;
c. administering 18 F-fallypride into said subject in the absence of haloperidol;
d. measuring an imaging signal of 18 F-fallypride in the pancreas of said subject in the absence of haloperidol;
e. detecting the level of Dopamine receptor expression in endocrine pancreatic islets by subtracting the imaging signal in the presence of haloperidol from the imaging signal in the absence of haloperidol;
and wherein the reduction in beta cell mass is predictive of being at risk or predisposed to developing clinical symptoms of diabetes in the subject.
2. The non-invasive method of claim 1 , wherein said imaging signals of said 18 F-fallypride is measured by positron emission tomography (PET) or positron emission tomography-computerized tomography (PET/CT) or positron emission tomography-magnetic resonance imaging (PET/MRI).
3. The method of claim 1 , wherein said subject is at preclinical stage of diabetes.
4. The method of claim 3 , wherein said diabetes is Type 1 or Type II diabetes.
5. The method of claim 1 , wherein said subject is at clinical stage of diabetes.
6. The method of claim 5 , wherein said diabetes is Type I or Type II diabetes.
7. The method of claim 1 wherein said subject is at preclinical stage or clinical stage of a diabetes-related metabolic syndrome.
8. The method of claim 1 wherein the administrations of 18 F-fallypride are administered with glucose.
9. The method of claim 1 wherein an oral glucose test is conducted simultaneously.
10. The non-invasive method of claim 1 , wherein said Dopamine receptor is D2 receptor.